Clinical Studies: Ultrastructural study of cerebral biopsies and autopsy material from cases of severe psychomotor retardation, multiple sclerosis and post-infectious encephalomyelitis will be performed. Experimental Studies: (1) Development of rat cortical synapses will be studied in situ and in synaptosomal fractions by ultrastructural morphometric methods, and activities of marker enzymes in fractions, during the period or neonatal maturation of the cerebral cortex. Similar studies will be performed in hypothyroid rats. (2) Cellular studies will be performed in experimental allergic encephalomyelitis (EAE); an attempt will be made to define the nature of the "effector" cell in EAE, and its production, distribution and circulation. Myelin basic protein will be used as antigen. Antibody-forming cells against basic protein (B cells) will be identified by their binding of radioiodinated basic protein (autoradiography) or by the use of basic protein peroxidase conjugates (cytochemistry). In vitro blastic transformation by basic protein of lymphoid cells of immunized animals will be used as assay of T cells. Cellular studies will be correlated with severity of histologically proven EAE, and circulating antibodies (radioimmuno assay or coprecipitation). Lymphoid cells from draining lymph nodes, thoracic duct or peripheral blood of animals with EAE will be introduced into organotypic CNS cultures and in vitro cytotoxicity will be evaluated. Cytotoxicity will be related to numbers of antibody- containing cells (Bcells) and cells undergoing blastic transformation (presumed T "effector" cells). A search for cells with a surface receptor for BP will be conducted. Cell surface interaction between lymphoid cells and target organ (oligodendroglia-myelin unit) will be examined in the in vitro system. (3) Methods of cell affinity labeling will be developed for detection of carbohydrate moities on lymphocytes, mouse neuroblastoma, normal chicken neurons in dissociated cell cultures, and in synaptosomes. Lectinperoxidase conjugates will be used. (4) Surface immunoglobulins will be detected on normal and specifically stimulated lymphoid cells (EAE). Cap formation and internalization of labeled plasma membrane for IgG and IgM will be studied in the electron microscope.